Hair cell damage recruited Lgr5-expressing cells are hair cell progenitors in neonatal mouse utricle

Lin, Jinchao; Zhang, Xiaodong; Wu, Fengfang; Lin, Weinian

doi:10.3389/fncel.2015.00113

Cited by 13 publications

(8 citation statements)

References 43 publications

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“…7), their transcriptional activity may be uniquely restricted in extrastriolar SCs (Chang et al, 2018). Additionally, extrastriolar SCs may lack signals that promote proliferation downstream of YAP-TEAD signaling: Wnt is reported to control proliferation downstream of YAP in organoids derived from cochlear progenitors that express Lgr5 1 (Xia et al, 2020), and striolar SCs, which express Lgr5 1 are more responsive to Wnt than extrastriolar SCs (Lin et al, 2015;Wang et al, 2015a;You et al, 2018). Retinoic acid receptor signaling is elevated in the developing extrastriola (Ono et al, 2020) and could limit proliferation there, consistent with its reported role in promoting cell cycle exit and differentiation in neural progenitors (Janesick et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

YAP Mediates Hair Cell Regeneration in Balance Organs of Chickens, But LATS Kinases Suppress Its Activity in Mice

et al. 2020

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Loss of sensory hair cells causes permanent hearing and balance deficits in humans and other mammals, but for nonmammals such deficits are temporary. Nonmammals recover hearing and balance sensitivity after supporting cells proliferate and differentiate into replacement hair cells. Evidence of mechanical differences between those sensory epithelia and their supporting cells prompted us to investigate whether the capacity to activate YAP, an effector in the mechanosensitive Hippo pathway, correlates with regenerative capacity in acceleration-sensing utricles of chickens and mice of both sexes. After hair cell ablation, YAP accumulated in supporting cell nuclei in chicken utricles and promoted regenerative proliferation, but YAP remained cytoplasmic and little proliferation occurred in mouse utricles. YAP localization in supporting cells was also more sensitive to shape change and inhibition of MST1/2 in chicken utricles than in mouse utricles. Genetic manipulations showed that in vivo expression of the YAP-S127A variant caused robust proliferation of neonatal mouse supporting cells, which produced progeny that expressed hair cell markers, but proliferative responses declined postnatally. Expression of YAP-5SA, which more effectively evades inhibitory phosphorylation, resulted in TEAD-dependent proliferation of striolar supporting cells, even in adult utricles. Conditional deletion of LATS1/2 kinases abolished the inhibitory phosphorylation of endogenous YAP and led to striolar proliferation in adult mouse utricles. The findings suggest that damage overcomes inhibitory Hippo signaling and facilitates regenerative proliferation in nonmammalian utricles, whereas constitutive LATS1/2 kinase activity suppresses YAP-TEAD signaling in mammalian utricles and contributes to maintaining the proliferative quiescence that appears to underlie the permanence of sensory deficits.

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Section: Discussionmentioning

confidence: 99%

YAP Mediates Hair Cell Regeneration in Balance Organs of Chickens, But LATS Kinases Suppress Its Activity in Mice

et al. 2020

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“…However, few CreER lines have been characterized for vestibular end organs, including the utricle. Four lines-Atoh1-CreER™, Lgr5 eGFP-CreERT2 , Plp-CreER T2 , and Sox2 CreERT2 -have been used to study hair cell regeneration or postnatal hair cell addition in neonatal utricles (Gómez-Casati et al 2010;Burns et al 2012a, b;Wang et al 2015;Lin et al 2015;Wu et al 2016). However, only two CreER lines have been described in the adult vestibular system.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Adult Vestibular Organs in 11 CreER Mouse Lines

Stone

Wisner

Bucks

et al. 2018

JARO

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Utricles are vestibular sense organs that encode linear head movements. They are composed of a sensory epithelium with type I and type II hair cells and supporting cells, sitting atop connective tissue, through which vestibular nerves project. We characterized utricular Cre expression in 11 murine CreER lines using the ROSA26 reporter line and tamoxifen induction at 6 weeks of age. This characterization included Calbindin2, Fgfr3-iCreER, GFAP-A-CreER™, GFAP-B-CreER™, GLAST-CreER, Id2, Otoferlin, Parvalbumin, Prox1, Sox2, and Sox9-CreER. Otoferlin mice had inducible Cre activity specific to hair cells. GLAST-CreER, Id2, and Sox9-CreER had inducible Cre activity specific to supporting cells. Sox2 had inducible Cre activity in supporting cells and most type II hair cells. Parvalbumin mice had small numbers of labeled vestibular nerve afferents. Calbindin2 mice had labeling of most type II hair cells and some type I hair cells and supporting cells. Only rare (or no) tdTomato-positive cells were detected in utricles of Fgfr3-iCreER, GFAP-A-CreER™, GFAP-B-CreER™, and Prox1 mice. No Cre leakiness (tdTomato expression in the absence of tamoxifen) was observed in Otoferlin mice. A small degree of leakiness was seen in GLAST-CreER, Id2, Sox2, and Sox9-CreER lines. Calbindin2 mice had similar tdTomato expression with or without tamoxifen, indicating lack of inducible control under the conditions tested. In conclusion, 5 lines-GLAST-CreER, Id2, Otoferlin, Sox2, and Sox9-CreER-showed cell-selective, inducible Cre activity with little leakiness, providing new genetic tools for researchers studying the vestibular periphery.

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“…Leucine-rich repeat-containing G-protein coupled receptors (LGRs) are also allegedly involved in hair cell regeneration. In particular, Lin et al [48] suggested that LGR5 positive cells may serve as hair cell progenitors in the mammalian cochlea. Retinoblastoma 1 (RB1) is an endogenous protein that regulating cellular proliferation and differentiation.…”

Section: A) Endogenous Stem Cellmentioning

confidence: 99%

Age-Related Hearing Loss: Recent Findings and Emerging Questions

Rodríguez

2020

SJO

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Age-related hearing loss (ARHL) or presbycusis is the most prevalent sensory deficit in the elderly. This progressive hearing impairment leads to social isolation. Currently, our understanding of ARHL is very limited. In this review, we have chosen to focus on recent work that has improved our understanding of the cellular and molecular mechanisms that may cause age-related loss of sensory and neural cells in the cochlea. Our goal here is to give an overview of recent progress towards understanding these phenomena. In addition, we discuss future prospects for advances in our understanding of genetic susceptibility, pathology, and potential therapeutic approaches in ARHL.

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Hair cell damage recruited Lgr5-expressing cells are hair cell progenitors in neonatal mouse utricle

Cited by 13 publications

References 43 publications

YAP Mediates Hair Cell Regeneration in Balance Organs of Chickens, But LATS Kinases Suppress Its Activity in Mice

YAP Mediates Hair Cell Regeneration in Balance Organs of Chickens, But LATS Kinases Suppress Its Activity in Mice

Characterization of Adult Vestibular Organs in 11 CreER Mouse Lines

Age-Related Hearing Loss: Recent Findings and Emerging Questions

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